RUBCN

Chr 3AR

rubicon autophagy regulator

Also known as: KIAA0226, RUBICON, SCAR15

NCBI Gene: 9711 ENSG00000145016 UniProt: Q92622 OMIM: 613516

The encoded protein negatively regulates autophagy by inhibiting PIK3C3 activity and controls endosome maturation and degradative endocytic trafficking. Mutations cause spinocerebellar ataxia, autosomal recessive 15, which primarily affects cerebellar function and coordination. This follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a negative regulator of autophagy and endocytic trafficking and controls endosome maturation. This protein contains two conserved domains, an N-terminal RUN domain and a C-terminal DUF4206 domain. The RUN domain is involved in Ras-like GTPase signaling, and the DUF4206 domain contains a diacylglycerol (DAG) binding-like motif. Mutation in this gene results in deletion of the DAG binding-like motif and causes a recessive ataxia. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.791 OMIM phenotype

Clinical Summary— RUBCN

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 157 VUS of 268 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.79LOEUF

pLI 0.000

Z-score 2.78

OE 0.58 (0.43–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.47Z-score

OE missense 0.83 (0.77–0.89)

472 obs / 570.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.43–0.79)

0≤0.351.4

Missense OE?0.83 (0.77–0.89)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 29 / 50.3Missense obs/exp: 472 / 570.7Syn Z: 0.98

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedRUBCN-related syndromic intellectual disability with ataxia, dysarthria and epilepsyOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6552th %ile

GOF

0.5562th %ile

LOF

0.3842th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

268 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic3

VUS157

Likely Benign50

Benign16

Conflicting7

Pathogenic

Likely Pathogenic

157

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	0	2
Likely Pathogenic	3	0	0	0	3
VUS	4	149	4	0	157
Likely Benign	0	14	8	28	50
Benign	0	7	1	8	16
Conflicting	—				7
Total	9	170	13	36	235

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

44 pathogenic / likely-pathogenic (of 67) ClinVar copy-number / structural variants overlap RUBCN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →